Browsing by Subject "Bronchopulmonary dysplasia"

Now showing 1 - 10 of 23
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    Acute Kidney Injury and Bronchopulmonary Dysplasia in Premature Neonates Born Less than 32 Weeks’ Gestation
    (Thieme, 2020-02) Starr, Michelle C.; Boohaker, Louis; Eldredge, Laurie C.; Menon, Shina; Griffin, Russell; Mayock, Dennis E.; Li, Linzi; Askenazi, David; Hingorani, Sangeeta; Pediatrics, School of Medicine
    Objective: This study aimed to evaluate the association between acute kidney injury (AKI) and bronchopulmonary dysplasia (BPD) in infants born <32 weeks of gestational age (GA). Study design: Present study is a secondary analysis of premature infants born at <32 weeks of GA in the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) retrospective cohort (n = 546). We stratified by gestational age and used logistic regression to determine association between AKI and moderate or severe BPD/mortality. Results: Moderate or severe BPD occurred in 214 of 546 (39%) infants, while death occurred in 32 of 546 (6%); the composite of moderate or severe BPD/death occurred in 246 of 546 (45%). For infants born ≤29 weeks of gestation, the adjusted odds ratio (OR) of AKI and the primary outcome was 1.15 (95% confidence interval [CI] = 0.47-2.86; p = 0.76). Infants born between 29 and 32 weeks of gestation with AKI had four-fold higher odds of moderate or severe BPD/death that remained after controlling for multiple factors (adjusted OR = 4.21, 95% CI: 2.07-8.61; p < 0.001). Conclusion: Neonates born between 29 and 32 weeks who develop AKI had a higher likelihood of moderate or severe BPD/death than those without AKI. Further studies are needed to validate our findings and evaluate mechanisms of multiorgan injury.
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    Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates
    (American Medical Association, 2023-08-01) Starr, Michelle C.; Griffin, Russell L.; Harer, Matthew W.; Soranno, Danielle E.; Gist, Katja M.; Segar, Jeffrey L.; Menon, Shina; Gordon, Lindsey; Askenazi, David J.; Selewski, David T.; Pediatrics, School of Medicine
    Importance: Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. Objective: To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. Design, setting, and participants: This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Exposure: Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). Main outcomes and measures: The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Results: A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). Conclusions and relevance: In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance.
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    All trans-retinoic acid modulates hyperoxia-induced suppression of NF-kB-dependent Wnt signaling in alveolar A549 epithelial cells
    (Public Library of Science, 2022-08-10) Tsotakos, Nikolaos; Ahmed, Imtiaz; Umstead, Todd M.; Imamura, Yuka; Yau, Eric; Silveyra, Patricia; Chroneos, Zissis C.; Medicine, School of Medicine
    Introduction: Despite recent advances in perinatal medicine, bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth. Inflammation, the main cause for BPD, results in arrested alveolarization. All trans-retinoic acid (ATRA), the active metabolite of Vitamin A, facilitates recovery from hyperoxia induced cell damage. The mechanisms involved in this response, and the genes activated, however, are poorly understood. In this study, we investigated the mechanisms of action of ATRA in human lung epithelial cells exposed to hyperoxia. We hypothesized that ATRA reduces hyperoxia-induced inflammatory responses in A549 alveolar epithelial cells. Methods: A549 cells were exposed to hyperoxia with or without treatment with ATRA, followed by RNA-seq analysis. Results: Transcriptomic analysis of A549 cells revealed ~2,000 differentially expressed genes with a higher than 2-fold change. Treatment of cells with ATRA alleviated some of the hyperoxia-induced changes, including Wnt signaling, cell adhesion and cytochrome P450 genes, partially through NF-κB signaling. Discussion/conclusion: Our findings support the idea that ATRA supplementation may decrease hyperoxia-induced disruption of the neonatal respiratory epithelium and alleviate development of BPD.
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    Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants
    (American Thoracic Society, 2017-08-01) Morrow, Lindsey A.; Wagner, Brandie D.; Ingram, David A.; Poindexter, Brenda B.; Schibler, Kurt; Cotten, C. Michael; Dagle, John; Sontag, Marci K.; Mourani, Peter M.; Abman, Steven H.; Pediatrics, School of Medicine
    RATIONALE: Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood. OBJECTIVES: To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g. METHODS: Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age. MEASUREMENTS AND MAIN RESULTS: After adjusting for covariates, we found that maternal smoking prior to preterm birth increased the odds of having an infant with BPD by twofold (P = 0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the neonatal intensive care unit admission. Preexisting hypertension was associated with a twofold (P = 0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. Twenty-two percent of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. CONCLUSIONS: We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking not only will lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth.
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    Assessment of inhibited alveolar-capillary membrane structural development and function in bronchopulmonary dysplasia
    (Wiley, 2014-03) Ahlfeld, Shawn K.; Conway, Simon J.; Department of Medicine, IU School of Medicine
    Bronchopulmonary dysplasia (BPD) is a chronic lung disease of extreme prematurity and is defined clinically by dependence on supplemental oxygen due to impaired gas exchange. Optimal gas exchange is dependent on the development of a sufficient surface area for diffusion. In the mammalian lung, rapid acquisition of distal lung surface area is accomplished in neonatal and early adult life by means of vascularization and secondary septation of distal lung airspaces. Extreme preterm birth interrupts secondary septation and pulmonary capillary development and ultimately reduces the efficiency of the alveolar-capillary membrane. Although pulmonary health in BPD infants rapidly improves over the first few years, persistent alveolar-capillary membrane dysfunction continues into adolescence and adulthood. Preventative therapies have been largely ineffective, and therapies aimed at promoting normal development of the air-blood barrier in infants with established BPD remain largely unexplored. The purpose of this review will be: (1) to summarize the histological evidence of aberrant alveolar-capillary membrane development associated with extreme preterm birth and BPD, (2) to review the clinical evidence assessing the long-term impact of BPD on alveolar-capillary membrane function, and (3) to discuss the need to develop and incorporate direct measurements of functional gas exchange into clinically relevant animal models of inhibited alveolar development.
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    Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial
    (American Medical Association, 2022-12-01) Starr, Michelle C.; Griffin, Russell; Gist, Katja M.; Segar, Jeffrey L.; Raina, Rupesh; Guillet, Ronnie; Nesargi, Saudamini; Menon, Shina; Anderson, Nekayla; Askenazi, David J.; Selewski, David T.; Pediatrics, School of Medicine
    Importance: Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population. Objective: To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates. Design, setting, and participants: This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021. Exposures: Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB. Main outcomes and measures: The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death. Results: A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51). Conclusions and relevance: In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes.
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    Bronchopulmonary Dysplasia: Executive Summary of a Workshop
    (Elsevier, 2018-06) Higgins, Rosemary D.; Jobe, Alan H.; Koso-Thomas, Marion; Bancalari, Eduardo; Viscardi, Rose M.; Hartert, Tina V.; Ryan, Rita M.; Kallapur, Suhas G.; Steinhorn, Robin H.; Konduri, Girija G.; Davis, Stephanie D.; Thebaud, Bernard; Clyman, Ronald I.; Collaco, Joseph M.; Martin, Camilia R.; Woods, Jason C.; Finer, Neil N.; Raju, Tonse N. K.; Pediatrics, School of Medicine
    Comment in Bronchopulmonary Dysplasia: The Ongoing Search for One Definition to Rule Them All. [J Pediatr. 2018] Midlife crisis? In its 50th year, BPD redefines itself. [J Pediatr. 2018]
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    Characteristics of Infants/Children Presenting to Outpatient Bronchopulmonary Dysplasia Clinics in the United States
    (Wiley, 2021) Collaco, Joseph M.; Agarwal, Amit; Austin, Eric D.; Hayden, Lystra P.; Lai, Khanh; Levin, Jonathan; Manimtim, Winston M.; Moore, Paul E.; Sheils, Catherine A.; Tracy, Michael C.; Alexiou, Stamatia; Baker, Christopher D.; Cristea, A. Ioana; Fierro, Julie L.; Rhein, Lawrence M.; Villafranco, Natalie; Nelin, Leif D.; McGrath-Morrow, Sharon A.; Pediatrics, School of Medicine
    Introduction: Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics. Methods: Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (<37 weeks) and respiratory symptoms or needs requiring outpatient follow-up. Results: A total of 413 preterm infants and children were recruited (mean age: 2.4 ± 2.7 years) with a mean gestational age of 27.0 ± 2.8 weeks and a mean birthweight of 951 ± 429 grams of whom 63.7% had severe BPD. Total, 51.1% of subjects were nonwhite. Severe BPD was not associated with greater utilization of acute care/therapies compared to non-severe counterparts. Of children with severe BPD, differences in percentage of those on any home respiratory support (p = .001), home positive pressure ventilation (p = .003), diuretics (p < .001), inhaled corticosteroids (p < .001), and pulmonary vasodilators (p < .001) were found between centers, however no differences in acute care use were observed. Discussion: This examination of a multicenter collaborative registry of children born prematurely with respiratory disease demonstrates a diversity of management strategies among geographically distinct tertiary care BPD centers in the United States. This study reveals that the majority of children followed in these clinics were nonwhite and that neither variation in management nor severity of BPD at 36 weeks influenced outpatient acute care utilization. These findings suggest that post-neonatal intensive care unit factors and follow-up may modify respiratory outcomes in BPD, possibly independently of severity.
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    Daycare Attendance is linked to Increased Risk of Respiratory Morbidities in Preterm Children with Bronchopulmonary Dysplasia
    (Elsevier, 2022) McGrath-Morrow, Sharon A.; Agarwal, Amit; Alexiou, Stamatia; Austin, Eric D.; Fierro, Julie L.; Hayden, Lystra P.; Lai, Khanh; Levin, Jonathan C.; Manimtim, Winston M.; Moore, Paul E.; Rhein, Lawrence M.; Rice, Jessica L.; Sheils, Catherine A.; Tracy, Michael C.; Bansal, Manvi; Baker, Christopher D.; Cristea, A. Ioana; Popova, Antonia P.; Siddaiah, Roopa; Villafranco, Natalie; Nelin, Leif D.; Collaco, Joseph M.; Pediatrics, School of Medicine
    Objectives: To test the hypothesis that daycare attendance among children with bronchopulmonary dysplasia (BPD) is associated with increased chronic respiratory symptoms and/or greater health care use for respiratory illnesses during the first 3 years of life. Study design: Daycare attendance and clinical outcomes were obtained via standardized instruments for 341 subjects recruited from 9 BPD specialty clinics in the US. All subjects were former infants born preterm (<34 weeks) with BPD (71% severe) requiring outpatient follow-up between 0 and 3 years of age. Mixed logistic regression models were used to test for associations. Results: Children with BPD attending daycare were more likely to have emergency department visits and systemic steroid usage. Children in daycare up to 3 years of age also were more likely to report trouble breathing, having activity limitations, and using rescue medications when compared with children not in daycare. More severe manifestations were found in children attending daycare between 6 and 12 months of chronological age. Conclusions: In this study, children born preterm with BPD who attend daycare were more likely to visit the emergency department, use systemic steroids, and have chronic respiratory symptoms compared with children not in daycare, indicating that daycare may be a potential modifiable risk factor to minimize respiratory morbidities in children with BPD during the preschool years.
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    Design and implementation of a multicenter protocol to obtain impulse oscillometry data in preterm children
    (Wiley, 2024-09-25) Tsukahara, Katharine; Ren, Clement L.; Allen, Julian; Bann, Carla; McDonough, Joseph; Ziolkowski, Kristina; Clem, Charles C.; DeMauro, Sara B.; Pediatrics, School of Medicine
    Importance: Objective measures of lung function are critical for assessing respiratory outcomes of prematurity. Among extremely low gestational age neonates (ELGANs) (< 29 weeks gestational age), high rates of neurodevelopmental impairment may interfere with lung function testing. Impulse oscillometry (IOS) is a noninvasive test of respiratory system mechanics not requiring forced expiration. Objective: To describe a multicenter study design for respiratory follow-up testing in a cohort with a high rate of extreme prematurity. Methods: School-age children enrolled in two prior trials of ELGANs and term controls were assessed by IOS at five centers. Groups consisted of children with prematurity with a high incidence of bronchopulmonary dysplasia, children with prematurity with no or minimal lung disease, and healthy term children. A rigorous centralized review process reviewed IOS studies for technical acceptability. Approach to design and implementation, rates of feasibility and success, and characteristics of participants are described. Results: A total of 243 children were recruited, of whom 239 (98%) attempted oscillometry. There were high rates of technical acceptability across all three cohorts (85%-90% of attempted tests), and across all five centers (80%-94% of attempted tests). Respiratory and neuromotor clinical factors associated with testing failure included a higher number of days on ventilation during neonatal intensive care, a history of intraventricular hemorrhage grade 3 or 4, and gross motor functional impairment. Interpretation: We report high rates of feasibility and success of oscillometry in a large multicenter ELGAN population, in whom neurological and developmental comorbidities likely play a confounding role.